Contributions of the Peroxisome and β-Oxidation Cycle to Biotin Synthesis in Fungi

Magliano, Pasqualina; Flipphi, Michel; Arpat, Alaaddin Bulak; Delessert, Syndie; Poirier, Yves

doi:10.1074/jbc.m111.279687

Cited by 35 publications

(26 citation statements)

References 37 publications

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“…Finally, we also considered biotin to be a rescue factor for the mfe2⌬ mutant because the biotin biosynthetic pathway in fungi might be located in the peroxisome and its precursor (pimelic acid) might depend on ␤-oxidation activity (46). In a spot test, we found that biotin also showed a weak rescue activity for the mfe2⌬ mutant (Fig.…”

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confidence: 86%

Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

2012

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ABSTRACTAn understanding of the connections between metabolism and elaboration of virulence factors during host colonization by the human-pathogenic fungusCryptococcus neoformansis important for developing antifungal therapies. Lipids are abundant in host tissues, and fungal pathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial β-oxidation pathways to utilize this potential carbon source. In addition, lipids are important signaling molecules in both fungi and mammals. In this report, we demonstrate that defects in the peroxisomal and mitochondrial β-oxidation pathways influence the growth ofC. neoformanson fatty acids as well as the virulence of the fungus in a mouse inhalation model of cryptococcosis. Disease attenuation may be due to the cumulative influence of altered carbon source acquisition or processing, interference with secretion, changes in cell wall integrity, and an observed defect in capsule production for the peroxisomal mutant. Altered capsule elaboration in the context of a β-oxidation defect was unexpected but is particularly important because this trait is a major virulence factor forC. neoformans. Additionally, analysis of mutants in the peroxisomal pathway revealed a growth-promoting activity forC. neoformans, and subsequent work identified oleic acid and biotin as candidates for such factors. Overall, this study reveals that β-oxidation influences virulence inC. neoformansby multiple mechanisms that likely include contributions to carbon source acquisition and virulence factor elaboration.

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confidence: 86%

Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

2012

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“…In addition, the fast-growing biotin-prototrophic strains described in this study provide interesting experimental platforms for unraveling the elusive biochemistry of pimelate biosynthesis in S. cerevisiae and other yeasts (10,12,13).…”

Section: Discussionmentioning

confidence: 99%

“…Starting from pimelic acid, biotin biosynthesis in prototrophic yeast strains follows the prokaryotic pathway ( Fig. 1), but the yeast pathway for synthesis of this key precursor has not yet been fully elucidated (10,12,13). Biotin biosynthesis genes in yeast are assumed to have been at least partially acquired from anaerobic bacteria by horizontal gene transfer, followed by gene duplication and neofunctionalization events (14,15).…”

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confidence: 99%

Laboratory Evolution of a Biotin-Requiring Saccharomyces cerevisiae Strain for Full Biotin Prototrophy and Identification of Causal Mutations

Bracher

Hulster

Koster

et al. 2017

Appl Environ Microbiol

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Biotin prototrophy is a rare, incompletely understood, and industrially relevant characteristic of Saccharomyces cerevisiae strains. The genome of the haploid laboratory strain CEN.PK113-7D contains a full complement of biotin biosynthesis genes, but its growth in biotin-free synthetic medium is extremely slow (specific growth rate [] Ϸ 0.01 h Ϫ1 ). Four independent evolution experiments in repeated batch cultures and accelerostats yielded strains whose growth rates ( Յ 0.36 h Ϫ1 ) in biotin-free and biotin-supplemented media were similar. Whole-genome resequencing of these evolved strains revealed up to 40-fold amplification of BIO1, which encodes pimeloyl-coenzyme A (CoA) synthetase. The additional copies of BIO1 were found on different chromosomes, and its amplification coincided with substantial chromosomal rearrangements. A key role of this gene amplification was confirmed by overexpression of BIO1 in strain CEN.PK113-7D, which enabled growth in biotin-free medium ( ϭ 0.15 h Ϫ1 ). Mutations in the membrane transporter genes TPO1 and/or PDR12 were found in several of the evolved strains. Deletion of TPO1 and PDR12 in a BIO1-overexpressing strain increased its specific growth rate to 0.25 h Ϫ1 . The effects of null mutations in these genes, which have not been previously associated with biotin metabolism, were nonadditive. This study demonstrates that S. cerevisiae strains that carry the basic genetic information for biotin synthesis can be evolved for full biotin prototrophy and identifies new targets for engineering biotin prototrophy into laboratory and industrial strains of this yeast. IMPORTANCE Although biotin (vitamin H) plays essential roles in all organisms, not all organisms can synthesize this vitamin. Many strains of baker's yeast, an important microorganism in industrial biotechnology, contain at least some of the genes required for biotin synthesis. However, most of these strains cannot synthesize biotin at all or do so at rates that are insufficient to sustain fast growth and product formation. Consequently, this expensive vitamin is routinely added to baker's yeast cultures. In this study, laboratory evolution in biotin-free growth medium yielded new strains that grew as fast in the absence of biotin as in its presence. By analyzing the DNA sequences of evolved biotin-independent strains, mutations were identified that contributed to this ability. This work demonstrates full biotin independence of an industrially relevant yeast and identifies mutations whose introduction into other yeast strains may reduce or eliminate their biotin requirements.KEYWORDS Saccharomyces cerevisiae, adaptive laboratory evolution, biotin, prototrophy, reverse metabolic engineering, vitamin biosynthesis, whole-genome sequencing

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“…The first enzyme in biotin synthesis (BioF) is peroxisomal in plants and fungi [3,4], while the subsequent steps are mitochondrial. Moreover, peroxisomal β-oxidation is required for synthesis of the BioF substrate, pimeloyl-CoA [3,4].…”

Section: Functional Diversity Of Plant Peroxisomesmentioning

confidence: 99%

Plant peroxisomes: recent discoveries in functional complexity, organelle homeostasis, and morphological dynamics

Reumann

Bartel

2016

Current Opinion in Plant Biology

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Peroxisomes are essential for life in plants. These organelles house a variety of metabolic processes that generate and inactivate reactive oxygen species. Our knowledge of pathways and mechanisms that depend on peroxisomes and their constituent enzymes continues to grow, and in this review we highlight recent advances in understanding the identity and biological functions of peroxisomal enzymes and metabolic processes. We also review how peroxisomal matrix and membrane proteins enter the organelle from their sites of synthesis. Peroxisome homeostasis is regulated by specific degradation mechanisms, and we discuss the contributions of specialized autophagy and a peroxisomal protease to the degradation of entire peroxisomes and peroxisomal enzymes that are damaged or superfluous. Finally, we review how peroxisomes can flexibly change their morphology to facilitate inter-organellar contacts.

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Contributions of the Peroxisome and β-Oxidation Cycle to Biotin Synthesis in Fungi

Cited by 35 publications

References 37 publications

Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

Laboratory Evolution of a Biotin-Requiring Saccharomyces cerevisiae Strain for Full Biotin Prototrophy and Identification of Causal Mutations

Plant peroxisomes: recent discoveries in functional complexity, organelle homeostasis, and morphological dynamics

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